Reduced oxycodone brain delivery in rats due to lipopolysaccharide-induced inflammation: microdialysis insights into brain disposition and sex-specific pharmacokinetics.

ABSTRACT:

Background

Oxycodone, a widely used opioid analgesic, has an unbound brain-to-plasma concentration ratio (K_p,uu) greater than unity, indicating active uptake across brain barriers associated with the putative proton-coupled organic cation (H⁺/OC) antiporter system. With this study, we aimed to elucidate oxycodone's CNS disposition during lipopolysaccharide (LPS)-induced systemic inflammation in Sprague-Dawley rats.

Methods

Using brain microdialysis, we dynamically and simultaneously monitored unbound oxycodone concentrations in blood, striatum, lateral ventricle, and cisterna magna following intravenous administration of oxycodone post-LPS challenge.

Results

Our results indicated a reduced, sex-independent brain net uptake of oxycodone across the

SUBMITTER: Ballgren F 

PROVIDER: S-EPMC11613587 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature